Doxorubicin combined with celecoxib inhibits tumor growth of medullary thyroid carcinoma in xenografted mice.

Xianying Meng,Guibin Zheng,Renzhu Pang,Jie Li,Qiang Zhang,Tebo Hua,Shuai Yang

doi:10.3892/ol.2014.2050

Doxorubicin combined with celecoxib inhibits tumor growth of medullary thyroid carcinoma in xenografted mice.

Xianying Meng, Guibin Zheng + Show 5 more

Open Access

https://doi.org/10.3892/ol.2014.2050

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Abstract

The aim of the present study was to investigate the antitumor effect of celecoxib (CXB) combined with doxorubicin (DOX) on the subcutaneous xenograft tumor of medullary thyroid carcinoma in nude mice, and to analyze the possible mechanism of action. Nude mice with xenografted medullary thyroid carcinoma (MTC) were randomly divided into the control, CXB, DOX and DOX plus CXB groups, and the drug treatment was administered for three weeks. It was found that the tumor inhibition rates and the apoptosis index in the treatment groups were higher than in the control group (P<0.01), and that these values were higher in the combination group compared with the single-drug group (P<0.01). DOX alone upregulated the cyclooxygenase-2 and multidrug-resistance 1 expression levels, and the combination of CXB and DOX or CXB alone notably decreased the expression level of the two proteins compared with no treatment. The results of the present study provide evidence that a combination of DOX and CXB is a potential drug candidate for the treatment of MTC.

Highlights

Primary thyroid cancers account for 1% of all malignant tumors
To investigate whether DOX combined with CXB inhibits thyroid cancer cell proliferation, TT cells derived from poorly‐differentiated human medullary carcinoma cells were treated with CXB, DOX or CXB combined with DOX for 24, 48, and 72 h
The resistance of medullary thyroid carcinoma (MTC) to conventional chemotherapy drugs is the major reason for the high mortality rate of patients with MTC who fail to respond to surgery

Summary

Introduction

Primary thyroid cancers account for 1% of all malignant tumors. The life expectancy is generally high, these cancers cause more fatalities than all endocrine organ cancers [1]. Medullary thyroid carcinomas (MTCs) are the third most common of all the thyroid cancers and are responsible for ~3‐4% of all thyroid cancer cases [2]. A common discovery in MTCs that are diagnosed late is lymph node metastasis in the upper mediastinum and neck. Metastases occur in ~70% of patients with MTC who have a palpable thyroid nodule (>1.0 cm diameter) [3].

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